Abeona Therapeutics Inc. (Abeona) is a clinical-stage biopharmaceutical company developing cell and gene therapies for life-threatening diseases.
The company’s lead clinical program is for prademagene zamikeracel (‘pz-cel’), the company’s investigational autologous, COL7A1 gene-corrected epidermal sheets in development for recessive dystrophic epidermolysis bullosa (‘RDEB’). Pz-cel has been granted Orphan Drug and Rare Pediatric Disease (‘RPD’) designations by the U.S. Food and Drug Administrat...
Abeona Therapeutics Inc. (Abeona) is a clinical-stage biopharmaceutical company developing cell and gene therapies for life-threatening diseases.
The company’s lead clinical program is for prademagene zamikeracel (‘pz-cel’), the company’s investigational autologous, COL7A1 gene-corrected epidermal sheets in development for recessive dystrophic epidermolysis bullosa (‘RDEB’). Pz-cel has been granted Orphan Drug and Rare Pediatric Disease (‘RPD’) designations by the U.S. Food and Drug Administration (‘FDA’) and Orphan Drug Designation by the European Medicines Agency (‘EMA’).
The company plans to continue the development of adeno-associated virus (‘AAV’) based gene therapies designed to treat ophthalmic diseases with high unmet medical need using the novel AIM capsid platform that the company has exclusively licensed from the University of North Carolina at Chapel Hill (‘UNC’), and internal AAV vector research programs. Abeona’s novel, next-generation AAV capsids are being evaluated to improve tropism profiles for a variety of devastating diseases.
Strategy
Abeona is a fully-integrated cell and gene therapy company featuring research and clinical development programs, in-house manufacturing facilities, and scientific and clinical leadership.
In September 2023, the company submitted a Biologics License Application (‘BLA’) for pz-cel to the FDA. In November 2023, the FDA accepted and granted priority review for the company’s BLA for pz-cel. Under the Prescription Drug User Fee Act (‘PDUFA’), the FDA has set a target action date of May 25, 2024.
The company partner with leading academic researchers, patient advocacy organizations, caregivers and other biotechnology companies to develop therapies that address the underlying cause of a broad spectrum of rare genetic diseases for which no effective treatment options exist today.
The company’s strategy consists of advancing and commercializing the company’s late-stage clinical cell and gene therapy programs with a focus on life-threatening diseases. developing novel in-vivo gene therapies using aim capsid technology. leveraging the company’s leadership position in commercial-scale cell and gene therapy manufacturing. establishing additional cell and gene therapy franchises and adjacencies through in-licensing and strategic partnerships. maintaining and growing the company’s IP portfolio.
Developing Next-Generation Cell and Gene Therapy
Pz-cel for the Treatment of RDEB
In the company’s VIITAL phase 3 and phase 1/2a clinical trials, pz-cel was applied as a one-time surgical procedure onto RDEB wounds and has shown up to 8 years of durable wound healing and associated pain reduction even in the toughest-to-treat in RDEB wounds. Patients evaluated in the VIITAL phase 3 trial had large wounds (> 20cm2) and, on average, had wounds remained open for 6.2 years, and in some cases up to 21 years, prior to pz-cel treatment. Most RDEB patients have large and chronic wounds that carry the highest burden, including the need for frequent dressing changes, pain, pruritus, risk of infection, and developing skin cancer.
Program Status
Pz-cel is the company’s investigational autologous epidermal sheets in which a functioning COL7A1 gene is inserted into a patient’s own skin cells (keratinocytes) using a retrovirus. The keratinocytes are then grown into credit card sized sheets and surgically applied to the patient to restore Type VII collagen expression and skin function.
Results from a completed Phase 1/2a study that enrolled seven patients with large and chronic RDEB wounds at Stanford University showed that pz-cel was well-tolerated and resulted in significant and durable wound healing (Siprashvili, Z., et al., 2016), with up to eight years of follow-up (So. Y, Nazaraoff, et al., Orphanet Journal Rare Disease 2022). To date, there have been no reported serious adverse events.
In November 2022, the company announced positive topline data from the company’s VIITAL study. The pivotal phase 3 VIITAL study evaluated the efficacy, safety, and tolerability of pz-cel in 43 large chronic wound pairs in 11 subjects with RDEB. The large chronic wounds randomized and treated in VIITAL measured greater than 20 cm2 of surface area and had remained open for a minimum of six months and a maximum of 21 years (mean 6.2 years). The co-primary endpoints of the study were: (1) the proportion of RDEB wound sites with greater than or equal to 50% healing from baseline, comparing randomized treated with matched untreated (control) wound sites at the six-month timepoint, as determined by direct investigator assessment; and (2) pain reduction associated with wound dressing change assessed by the mean differences in scores of the Wong-Baker FACES Pain Rating Scale between randomized treated and matched untreated (control) wounds at the six-month timepoint.
The VIITAL study met its two co-primary efficacy endpoints demonstrating statistically significant, clinically meaningful improvements in wound healing and pain reduction in large chronic RDEB wounds. Pz-cel was shown to be well-tolerated with no serious treatment-related adverse events observed, consistent with past clinical experience. There were no deaths or instances of positive replication-competent retrovirus results, and no systemic immunologic responses were reported during the study, as well as no squamous cell carcinoma at treatment sites after application of pz-cel. Two subjects reported at least one serious adverse event unrelated to pz-cel. Four subjects reported related treatment emergent adverse events, including procedural pain, muscle spasms and pruritis. Infections unrelated to pz-cel were observed in eight patients.
In September 2023, the company submitted a BLA for pz-cel to the FDA. In November 2023, the FDA accepted for filing and granted priority review for the company’s BLA for pz-cel. Under the PDUFA, the FDA has set a target action date of May 25, 2024. Pz-cel has been granted Regenerative Medicine Advanced Therapy (‘RMAT’), Breakthrough Therapy, Orphan Drug and RPD designations by the by the FDA as well as Orphan Drug designation by the EMA.
Among the potential benefits of Orphan Drug designation are a potential seven years of market exclusivity following FDA approval, potentially preventing FDA approval of another product deemed to be the same as the approved product for the same indication, waiver of application fees, and tax credits for qualified clinical testing expenses conducted after orphan designation is received. A sponsor who receives an approval for a BLA with RPD designation may qualify for a Priority Review Voucher (‘PRV’), subject to final determination by the FDA. A PRV may be used to receive expedited review of a subsequent marketing application for a different product or sold to another company.
The company has continued to prepare its cGMP commercial facility in Cleveland for manufacturing pz-cel to support the company’s planned BLA filing. Pz-cel study drug product for all the company’s VIITAL study participants has been manufactured at the company’s Cleveland facility.
ABO-503 for the Treatment of X-linked Retinoschisis (‘XLRS’)
ABO-503, composed of a functional human RS1 packaged in the novel AIM capsid AAV204, has shown preclinical efficacy following delivery to the retina in a mouse model of XLRS. Preclinical studies have demonstrated robust RS1 expression in the retina, improved cone photoreceptor density and overall photoreceptor cell survival, as well as a restoration of outer retina architecture. Results of these studies were presented at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting in May 2023. A pre-IND meeting for ABO-503 was conducted with the FDA in April 2023 and provided Abeona with comprehensive feedback to support a future IND submission.
ABO-504 for the Treatment of Stargardt Disease
Abeona’s internal research and development team developed ABO-504, which is designed to efficiently reconstitute the full-length ABCA4 gene by implementing a dual AAV vector strategy using the Cre-LoxP recombinase system. Abeona previously reported preclinical data demonstrating the ability of the dual AAV vector system to produce full length ABCA4 protein in cell culture. Recent proof-of-concept studies, presented at the 2023 ASGCT Annual Meeting, have extended these findings by showing expression of ABCA4 mRNA and full-length ABCA4 protein in the retina of subretinally dosed abca4-/- knockout mice, at levels similar to endogenous ABCA4 in wild-type animals. A pre-IND meeting for ABO-504 was conducted with the FDA in June 2023 and provided Abeona with comprehensive feedback to support a future IND submission.
ABO-505 for the Treatment of Autosomal Dominant Optic Atrophy (‘ADOA’)
ABO-505 is designed to express a functional copy of human Opa1 in the retina following para-retinal injection. ABO-505 aims to take advantage of the robust optic nerve and RGC transduction ability of AAV204 to deliver its genetic payload to the cells most affected by ADOA. Preclinical studies have confirmed expression of Opa1 in both cell culture and the retinas of dosed wild-type and disease model animals. Initial efficacy results suggest an improvement in retinal signaling to the brain and improved visual acuity in treated mutant mice. These studies were presented at the ASGCT Annual Meeting in May 2023.
Gene Therapy Treatments anchored in AIM Vector Platform
In 2016, the company licensed a library of novel AAV capsids from UNC. The AIM vector system is a platform of AAV capsids capable of widespread central nervous system gene transfer and can be used to confer high transduction efficiency for various therapeutic indications. In partnership with academic institutions, the company’s own scientific research teams have identified vectors within the AIM capsid library showing strong potential to successfully target and reach the central nervous system, as well as ocular, lung, muscle, liver, and other tissues. Based on continuing research by Abeona and the company’s research partners, the company has observed improvements in gene delivery to specific tissues compared to available AAV technology. AIM vectors also have the potential for redosing subjects who previously received certain AAV gene therapy or subjects who have pre-existing antibodies to naturally occurring AAV serotypes.
Strategic Licensing Agreements
The company has out-licensed certain clinical and research programs, including for the treatment of Sanfilippo syndrome type A (MPS IIIA) to Ultragenyx Pharmaceutical Inc. (‘Ultragenyx’), and for CLN1 disease (infantile Batten disease) and Rett syndrome to Taysha Gene Therapies, Inc. (‘Taysha’). Under the terms of the company’s agreement with Ultragenyx, the company is eligible to receive payments based on the achievement of certain sales milestones and royalties on net sales. Under the company’s agreements with Taysha, the company is eligible to receive payments based on certain clinical, regulatory, and sales milestones and royalties on net sales.
Leveraging Leadership Position in Commercial-Scale Cell and Gene-Therapy Manufacturing
The company has established a cGMP manufacturing facility, the Elisa Linton Center located in Cleveland, Ohio, which enables the company to enhance supply chain control, establish tighter quality control testing, increase supply capacity, reduce production costs and gain manufacturing efficiency for clinical trials related to the company’s product candidates and ensure commercial demand is met in the event the company’s therapies receive marketing approval. The company’s facility is led by a team of highly skilled production, process/assay development and quality control scientists with expertise in cell and gene therapy, particularly in cell culture, upstream manufacturing, downstream purification, assay development and wet lab techniques.
The company has completed its 16,000+ square foot manufacturing build-out in Cleveland, Ohio. The first phase, completed in 2018, was a 6,000 square foot state-of-the-art cGMP production facility for the manufacturing of cell and gene therapies. The facility is designed to initially manufacture clinical drug products with intent of manufacturing commercial grade cGMP drug product. The second phase, completed in 2019, was the completion of an additional 8,000 square feet of state-of-the-art laboratory space to support the company’s expanding quality control, process development, and assay development teams. The second phase also included nearly 2,000 square feet of cGMP Inventory Control space.
The company has advanced its in-house manufacturing capabilities for pz-cel. The product is manufactured as a multilayer cellular sheet containing corrected keratinocytes that is fastened to a petrolatum gauze backing with surgical titanium ligating clips. Engineered sheets are applied over wound areas, where they provide keratinocytes with functional Type VII collagen, providing immediate wound coverage and allowing for long-term wound healing. A key component to the pz-cel drug product manufacturing process is the retroviral vector, which delivers the functional copy of the Collagen VII Alpha 1 cDNA to the autologous patient cells. Initially developed at the Indiana University Vector Production Facility, the company has transferred the cGMP manufacturing process for the LZRSE-Col7A1 retroviral vector to the company’s Cleveland facility and have demonstrated analytical comparability between IUVPF and Abeona-produced retroviral vector. In order to support licensure, the company has produced three cGMP process validation lots and has also created and characterized a cGMP master cell bank and a working cell bank to support the cGMP production of the retroviral vector.
The company has established AAV vector manufacturing capabilities that use the triple plasmid transient transfection method. The company inserts, or transfects, many copies of three DNA plasmids encoding the specific therapeutic gene sequence, or transgene, the capsid coding sequence, and helper sequences into AAV-293 cells using a serum-free, suspension-based bioreactor vector production technology. During an incubation period following transfection, each cell produces AAV vectors through biosynthesis using the cells’ natural machinery. At the end of the incubation period, the newly generated AAV vectors are harvested, filtered, and purified in a multi-step process.
The company has established and maintained strong and collaborative relationships with third-party companies specializing in the testing of cell and gene therapy material to complement the company’s process and assay development needs.
The company has made significant investments in developing optimized manufacturing processes and the company’s processes and methods developed to date provide a comprehensive manufacturing process for pz-cel and AAV-based vector therapies, including sufficient scale to support commercial manufacturing requirements for pz-cel; processes related to biopsy, cell collection, storage and transportation as part of manufacturing for pz-cel; processes related to product release testing for pz-cel; processes related to the manufacture and release testing of retroviral vector; establishing transportation and packaging processes and materials for finished pz-cel product; proprietary AAV vector manufacturing processes and techniques that produce a highly purified product candidate; AAV serum-free suspension technology that is readily scalable; multiple assays to accurately characterize the company’s process and the AAV vectors the company produces; and a series of purification processes, which may be adapted and customized for multiple different AAV capsids, with a goal of higher concentrations of active vectors, and that are essentially free of empty capsids.
These improvements will enable the company to develop best-in-class, next-generation cell and gene therapy products. As the company looks to commercialize pz-cel (subject to FDA approval), the company has filed its BLA to support commercial manufacturing of pz-cel from the company’s Cleveland facility.
Licensed Technologies and Intellectual Property
Recessive Dystrophic Epidermolysis Bullosa
To support the company’s EB franchise, the company has licensed a patent family from Stanford University covering pz-cel and its use in the treatment of RDEB. Patents covering the company’s investigational pz-cel product have been granted by the European Patent Office (EP3400287B1) and in other geographical regions, and are expected to expire in early 2037. Patent applications remain pending in the United States which, if granted, would be expected to expire in 2037. The company has also filed United States and Canadian patent applications directed to the packaging and transport of pz-cel, which, if granted, are not expected to expire before 2040.
The company may also rely on the additional protection afforded by data exclusivity (12 years for biologics like pz-cel), other market exclusivity such as orphan drug exclusivity (seven years), and patent term extensions, where applicable.
AIM Capsids
The company has an exclusive license to an international patent family from The University of North Carolina at Chapel Hill (‘UNC’) covering novel AAV capsids (‘AIM capsids’) that may potentially be used to deliver a wide variety of therapeutic transgenes to human cells to treat genetic diseases. National stage applications directed to the AIM capsids have been filed in the United States, Europe and other geographical regions. The first U.S. patent in this patent family, U.S. Patent No. 10,532,110 (the ‘‘110 Patent’), was issued to UNC on January 14, 2020. The ‘110 Patent is entitled to 352 days of patent term adjustment, making its projected expiration date November 6, 2036. The second U.S. patent in this patent family, U.S. Patent No. 10,561,743 (the ‘‘743 Patent’), was issued to UNC on February 18, 2020. The ‘743 Patent is expected to expire on November 20, 2035. A third U.S. patent in this patent family, U.S. Patent No. 11,491,242 (the ‘‘242 Patent’) issued on November 8, 2022. The ‘242 Patent is entitled to 429 days of patent term adjustment and will not expire before January 22, 2037. Patents have also been granted in Australia (AU2015349759B2), Israel (IL252072), and Russia (RU2727015). The company has exclusive rights to these patents under the company’s license with UNC.
The company also owns a second patent family directed to certain AAV capsids and have filed national stage applications in the United States, Europe and other geographical regions. Patents issuing from these applications are not expected to expire before 2039.
CLN1 Disease (Infantile Batten Disease)
The company has also licensed from UNC rights to two patent families directed to treating CLN1 disease (also known as infantile Batten disease). The first patent family is directed to optimized CLN1 genes and expression cassettes for use in treating CLN1 disease, which has applications pending in the United States, Europe, and other geographical regions. One U.S. patent in the first patent family, U.S. Patent No. 11,504,435 (the ‘‘435 Patent’), was issued to UNC on November 22, 2022. The ‘435 Patent is entitled to 578 days of patent term adjustment, making its projected expiration date January 12, 2039. The second patent family is directed to treating CLN1 disease using a combination of intrathecal and intravenous administrations, which has applications pending in the United States, Europe, and other geographical regions. Patents issuing from applications in the second patent family will have a 20-year expiration date of no earlier than 2040. The company has entered into agreements exclusively sublicensing these two CLN1 patent families to Taysha Gene Therapies, Inc.
Rett Syndrome
The company has licensed rights to one patent family from UNC and two patent families from The University Court of the University of Edinburgh (‘U. Edinburgh’) and The University Court of the University of Glasgow (‘U. Glasgow’) relating to gene therapy for the treatment of Rett Syndrome. The patent family licensed from UNC at Chapel Hill are directed to viral genomes designed to regulate expression of the MeCP2 gene, which is mutated in patients with Rett Syndrome. This patent family has pending applications in the United States, Europe and other geographical regions. Patents issuing from these applications will have a 20-year expiration date of no earlier than 2039. The patent families licensed from U. Edinburgh and U. Glasgow are directed to expression cassettes for MeCP2 polypeptides and to synthetic MeCP2 polypeptides. The patent family directed to MeCP2 expression cassettes has pending applications in the United States, Europe and other geographical regions. The patent family directed to synthetic MeCP2 polypeptides has pending applications in the United States and other geographical regions. Patents issuing from applications in the Edinburgh patent families will have a 20-year expiration date of no earlier than 2038. In October 2020, the company entered into an agreement exclusively sublicensing these UNC and University of Edinburgh patent rights to Taysha Gene Therapies.
Multipartite AAV Delivery of Large Transgenes
The company owns a patent family directed to multipartite delivery of large transgenes using AAV vectors and have filed national stage applications in the United States, Europe and other geographical regions. Patents issuing from these applications are not expected to expire before 2041.
The company also owns a pending U.S. provisional application directed to multipartite AAV delivery and its use for treating Stargardt disease.
New AAV Capsids and Ophthalmic Disease Treatment via Para-retinal AAV Administration
The company owns a patent family directed to (i) novel AAV capsid proteins and (ii) treating ophthalmic diseases via para-retinal administration of AAV vectors, and have filed national stage applications in the United States, Europe, and other geographical regions. Patents issuing from these applications are not expected to expire before 2042.
Treatment of Dominant Optic Atrophy and X-linked Retinoschisis
The company owns a pending PCT application (PCT/US2023/065877) directed to compositions and methods for treating dominant optic atrophy and x-linked retinoschisis. Patents issuing from future national stage applications of this PCT application are not expected to expire before 2043.
The U.S. Biologic Products Development Process
In addition, manufacturers and other entities involved in the manufacture and distribution of approved therapeutics are subject to periodic announced and unannounced inspections by the FDA and these state agencies for compliance with cGMP and other requirements, which impose certain procedural and documentation requirements upon the company and third-party manufacturers.
In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act and the Toxic Substances Control Act, affect the company’s business. These and other laws govern the use, handling and disposal of various biologic and chemical substances used in, and wastes generated by, operations.
To obtain regulatory approval of an investigational biologic product under European Union regulatory systems, applicants must submit a marketing authorization application (‘MAA’). The grant of marketing authorization in the European Union for products containing viable human tissues or cells such as gene therapy medicinal products is governed by Regulation 1394/2007/EC on advanced therapy medicinal products, read in combination with Directive 2001/83/EC of the European Parliament and of the Council, commonly known as the Community code on medicinal products and Regulation (EC) 726/2004 of the European Parliament and of the Council laying down Union procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency. Regulation 1394/2007/EC lays down specific rules concerning the authorization, supervision and pharmacovigilance of gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products. Manufacturers of advanced therapy medicinal products must demonstrate the quality, safety and efficacy of their products to the European Medicines Agency (‘EMA’) which provides an opinion regarding the application for marketing authorization. The European Commission grants or refuses marketing authorization in light of the opinion delivered by EMA.
Research and Development
For the year ended December 31, 2023, the company's total research and development expenses were $31.1 million.
History
The company was formerly known as Access Pharmaceuticals, Inc. and changed its name to PlasmaTech Biopharmaceuticals, Inc. in 2014. Further, it changed its name to Abeona Therapeutics Inc. in 2015.
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